Objective To observe the effect of resveratrol on multidrug resistance (MDR) in human retinoblastoma cells treated. Methods RB cells in logarithmic growth phase were divided into experimental group and control group. RB cells in experimental group were cultured with different concentrations of resveratrol (6.25, 12.50, 25.00, 50.00, 100.00 mu;mol/L) for 24 and 48 hours. The proliferation (absorbance value) was assayed using methyl thiazolyl tetrazolium (MTT). RB cells were cultured with 50.00 mu;mol/L resveratrol for 48 hours. The expressions of MDR-1, cyclooxygenase-2 (COX-2)、multidrug resistance-associated protein-1 (MRP-1), glutathione-S-transferases-pi; (GST-pi;) were determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. The RB cells of the control group were cultured with 0.5% dimethyl sulfoxide. Results Compared with the control group, the absorbance value decreased in experimental groups (6.25, 12.50, 25.00, 50.00 mu;mol/L) in a dose dependent manner (F=4.782，P＜0.05). The difference of absorbance value between 50.00 and 100.00 mu;mol/L experimental groups was not significant (F=6.351,P＞0.05). Compared with the control group, the mRNA (t=9.170, 5.758, 4.152, 4.638) and protein (t=3.848, 5.955, 4.541, 3.514) expression levels of MDR-1, MRP1, COX-2, and GST-pi; decreased in the experimental group (P＜0.05). Conclusion Resveratrol can down-regulate the expression of MDR in RB cells.
Objective To investigate the clinical manifestations,diagnosis and treatment of extensively drug-resistant tuberculosis (XDR-TB)meningitis. Methods One case of primary tuberculousis meningitis infected with multidrug-resistant mycobacteria was analyzed retrospectively.Relevant literatures were also reviewed by retrieving information through Wanfang Database and Pubmed using key words "multiple drug resistant tuberculosis meningitis","MDR tuberculosis meningitis","multiple drug resistant TBM","mul-drug resistant tuberculous meningitis","extensively drug resistant tuberculosis meningitis","XDR TBM","extensively drug resistant TBM" both in Chinese and English. Results A 24-year-old male patient,complained of headache,vomiting for 5 days,aggravated with mental abnormalities for 10 hours,with no history of pulmonary tuberculosis,was hospitalized in the Affiliated Hospital of Zunyi Medical College.The chest plain film was normal.Craniocerebral CT scan showed mild-hydrocephalus and cisterna ambiens stenosis.The patient died after undergoing anti-TB treatments with isoniazid(INH)0.3g iv qd,INH 0.3g po qd,rifampicin(RFP)0.45g qd,pyrazinamide(PZA)1.5g qd,ethambutol(EMB)0.75g qd,and dexamethasone(DEX)15mg qd.He was diagnosed as XDR-TB meningitis(as drug-resistant to isoniazid,rifampicin,streptomycin,ciprofloxacin,paminosalicylic acid,kanamycin,and protionamide ).Mycobacteria tuberculosis was isolated from his cerebrospinal fluid after 3 months.Five cases in 4 literatures were retrieved through Wanfang database and Pubmed among which 2 cases were initial treated,3 cases was unknown about initial treatment or re-treatment. Conclusions XDR-TB meningitis is rare in clinical practice with serious condition,rapid progress and high mortality rate.It is necessary to acquire drug susceptibility test results as soon as possible and adjust treatments according different conditions.A molecular drug susceptibility test may be helpful in the future.
Objective To study the efficacy and safety of combined anti-tuberculosis regimen containing bedaquiline in the treatment of multidrug-resistant tuberculosis (MDR-TB). Methods A total of 69 MDR-TB patients treated by joint regimen combined bedaquiline with other anti-tuberculosis drugs between March 2018 and August 2019 in Public Health Clinical Center of Chengdu were taken as the trial group, and 60 MDR-TB patients received treatment without bedaquiline between June 2016 and December 2017 in the same hospital were taken as the control group. The efficacy and safety of the two groups were compared. Results The 69 patients in the trial group included 44 males and 25 females, aged from 21 to 63 years, with an average of (34.6±11.0) years; 58 patients (84.1%) completed the 24-week treatment with bedaquiline, while 11 patients did not complete the treatment, including 3 deaths (4.3%), 1 loss of follow-up (1.4%), 1 withdrawal from the study (1.4%), and 6 discontinuation due to adverse events (8.7%). Among the 54 patients with positive results of tuberculosis on baseline sputum culture, 49 transformed to negative results within 24 weeks of treatment (the negative conversion rate was 90.7%), and the median negative conversion time was 13.0 weeks. The 60 patients in the control group included 45 males and 15 females, aged from 16 to 66 years, with an average of (35.5±13.2) years. Among the 53 patients with positive results of tuberculosis on baseline sputum culture, 30 transformed to negative results within 24 weeks of treatment (the negative conversion rate was 56.6%), and the median negative conversion time was 12.0 weeks. The negative conversion rate of sputum bacteria in the trial group was significantly higher than that in the control group (χ2=16.133, P<0.001). The most common adverse reactions in the trial group were liver function abnormalities (42 cases, 60.9%), prolonged QTc interval (37 cases, 53.6%), electrolyte disturbances (20 cases, 29.0%), and blood system damage (20 cases, 29.0%). In the 37 patients who experienced prolonged QTc interval, there were 8 patients with QTc intervals≥500 ms and 29 patients with QTc intervals ≥450 ms and <500 ms, with a median occurrence time of 16.0 weeks, among whom 25 patients experienced prolonged QTc interval in 4-48 weeks after the withdrawal of bedaquiline. Conclusion The negative conversion rate of tuberculosis sputum culture of patients with MDR-TB treated by bedaquiline combined with other anti- tuberculosis drugs is high, but electrocardiogram should be closely monitored during and after the treatment in order to guard against the potential cardiac toxic effects of bedaquiline.
ObjectiveTo explore the distribution and rule of pathogen strains in the third quarter and fourth quarter of 2012, and to provide the basis for clinical medication. MethodsTo retrospectively analyze the bacterial culture and drug susceptibility test results in the third quarter and the fourth quarter of 2012. ResultsThere were isolated 932 plants in the third quarter, and 915 plants isolated in the fourth quarter. Heavy drug resistance rates of detection of Pseudomonas aeruginosa decrease slightly. There was more multiple drug resistance of A. baumanii, Escherichia coli, Klebsiella pneumoniae, and methicillin-resistant Staphylococcus aureus in the fourth quarter than in the third one. ConclusionThe resistant strain increases in the fourth quarter. We should attach importance to the clinical examination, bacterial drug resistance monitoring, and rational use of antimicrobial agents.
【Abstract】ObjectiveTo establish adriamycin (ADM) resistant pancreatic cancer cell line SW1990/ADM and to investigate its drug resistance mechanism.MethodsADM-resistant pancreatic cancer cell line SW1990/ADM was obtained by culture of pancreatic cancer cell line SW1990 in vitro with intermittently increasing the concentration of ADM in the culture medium for ten months. After two months of drug free culture, its biological characteristics, drug sensitivity as well as the expression and function of multidrug resistant gene 1 (mdr1) were detected, respectively. ResultsCompared with the parental cell line, SW1990/ADM showed great changes in biological characteristics and developed a cross resistance to various chemotherapy drugs. The drug resistance indexes of cell line SW1990/ADM to ADM, mitomycin, fluorouracil and gemcitabine were 49.60, 7.25, 3.80 and 1.25, respectively. The level of mdr1 mRNA expression in cell line SW1990/ADM was much higher than that of the parental cell line（P＜0.01). ConclusionWe have established adriamycin resistant pancreatic cancer cell line SW1990/ADM with multidrug resistance phenotype, its multidrug resistance is positively relevant to the expression of mdr1.
ObjectiveTo understand the drug resistance of Mycobacterium tuberculosis complex in West China Hospital, Sichuan University, analyze its drug resistance characteristics, and provide reference for the monitoring of drug-resistant tuberculosis.MethodsFrom January 2016 to March 2018, Mycobacterium tuberculosis drug susceptibility testing kit was used to detect the drug susceptibility of Mycobacterium tuberculosis culture-positive strains in Department of Laboratory Medicine, West China Hospital, Sichuan University. The tested drugs included four of the first-line anti-tuberculosis drugs: rifampicin, isoniazid, ethambutol, and streptomycin, and ten of the second-line anti-tuberculosis drugs: capreomycin, ofloxacin, ethionamide, p-aminosalicylic acid, levofloxacin, moxifloxacin, rifabutin, amikacin, kanamycin, and chlorine phenazine.ResultsA total of 130 patients (130 strains) were enrolled, including 82 newly diagnosed patients (82 strains) and 48 re-treated patients (42 strains). The drug resistance rate of the 130 patients was 37.69%. The drug resistance rate of the newly diagnosed patients (28.05%) was significantly lower than that of the re-treated patients (54.17%), and there was a statistical difference (χ2=8.794, P=0.003). The multi-drug resistance rate of the newly diagnosed patients (6.10%) was significantly lower than that of the re-treated patients (25.00%), and the difference was statistically significant (χ2=9.517, P=0.002). The resistance rate of isoniazid, rifampicin, and streptomycin in newly diagnosed patients (23.17%, 8.54%, and 7.32%, respectively) were significantly lower than those in the re-treated patients (45.83%, 41.67%, and 29.17%, respectively), and the differences were statistically significant (P<0.05). The resistance rate of ofloxacin, moxifloxacin, rifabutin and ethionamide in the newly diagnosed patients (9.76%, 8.54%, 7.31%, and 4.88%, respectively) were significantly lower than those in the re-treated patients (39.58%, 27.08%, 25.00%, and 22.92%, respectively), and the differences were statistically significant (P<0.05).ConclusionIt is necessary to strengthen the standardized treatment of patients with newly diagnosed tuberculosis, increase the treatment and management of re-treated tuberculosis patients, and prevent the generation and spread of drug-resistant patients, especially multidrug-resistant patients.
Objective To review the clinical features and trend in antimicrobial resistance of Acinetobacter baumannii (A. baumannii) bloodstream infections. Methods Retrospective analysis was performed by collecting data of underlying diseases, potential risk factors, clinical characteristics, blood test results, Acute Physiology and Chronic Health EvaluationⅡ (APACHEⅡ) scores at onset, bacterial resistance to antibiotics and antimicrobial therapy were collected in Hunan Provincial People’s Hospital from January 2010 to June 2016. Results There were 114 non-duplicated A. baumannii complex blood isolates identified in this research. All patients had at least one underlying disease and accepted at least one surgery or invasive operation within the past 14 days. Multidrug-resistant A. baumannii (MDRAB) was isolated from 89 (78.1%) patients. Of the 114 strains of A. baumannii, 12.3% were resistant to tigecycline, 55.3% to amikacin and 61.4% to cefoperazone-sulbactam. The overall mortality was 51.8% (59/114). The patients with MDRAB had higher mortality rate than those with non-MDRAB (62.9% vs. 12.0%, χ2=20.268, P<0.001). With higher incidence of being in the intensive care unit, intubation/tracheotomy and increased APACHEⅡ score among patients with MDRAB bacteremia (P<0.05). Compared with subjects treated with tigecycline based regimen, those treated with non tigecycline for multidrug resistantA. baumannii had a higher mortality (64.8% vs. 60.0%) but there was no statistical significance (P>0.05). Conclusions The isolated A. baumannii are mainly multidrug resistant and with high mortality. Being in the intensive care unit, increased APACHEⅡ score and intubation/tracheotomy were risk factors for higher mortality among patients with MDRAB bloodstream infection. Tigecycline based regimen doesn’t improve patients’ prognosis.
ObjectTo investigate the pathogenesis of drug-resistant epilepsy by examining the expression of mRNA and protein of Cell Division Cycle 42 GTP-binding protein (Cdc42), Neural Wiskott-Aldrich Syndrome Protein (N-WASP) and Actin-related protein 2/3(Arp2/3) in peripheral blood of patients with drug-resistant epilepsy (DRE).MethodsSeventy two essential epilepsy patients who were attended at outpatients and inpatients in the Department of Neurology of the Affiliated Hospital of Youjiang Medical University for Nationalities were selected from October 2016 to October 2018. According to the 2010 International League Against Epilepsy’s definition of Drug-Resistant Epilepsy, the patients were divided into 2 groups: 32 patients with DRE were defined as DRE group, 40 patients with anti-epilepsy drugs (AEDs) well controlled were defined as the well controlled group. Thirty two healthy persons were selected as control group. The expression of mRNA and protein of Cdc42, N-WASP and Arp2/3 in peripheral blood were measured by quantitative real-time PCR (RT-qPCR) and Western blot(WB). Experimental data were analyzed by ANOVA or rank-sum test.ResultsCompared with well-controlled group and healthy persons group, Cdc42, N-WASP, Arp2/3 in DRE group were significantly increased, the differences were statistically significant (P<0.05). Compared with the control group, Cdc42, N-WASP, Arp2/3 in well-controlled group were significantly increased, with statistically significant differences (P<0.05).ConclusionThe expression of Cdc42, N-WASP, Arp2/3 in peripheral blood of patients with DRE significantly increased, being closely related to the occurrence and development of DRE, and used as indicators in peripheral blood predicting the occurrence of DRE.
Objective To establish a xenograft model of hydroxycamptothecine (HCPT)-resistant human gastric cancer cell line (SGC-7901/HCPT) in nude mice and study its biological characteristics. Methods The SGC-7901 and SGC-7901/ HCPT cells were cultured in vitro. The cell suspension was injected subcutaneously into the nude mice. When the subcutaneous carcinoma was 1.0 cm in diameter, it was cut off and divided into pieces of 0.1-0.2 cm in diameter． Then the small pieces of tumor were re-transplanted subcutaneously into the second generation nude mice until the fourth generation. The morphological feature, ultramicro-structure, and growth characteristics of the fourth generation transplanted tumor were examined. The drug resistance was measured by methyl thiazolyl tetrazolium (MTT) assay. Results The transplanted tumor in nude mice was round or oval, and many blood vessels were on its surface. Under the light microscope, the sizes of SGC-7901 transplanted tumor cells were similar, and sizes of cell nuclei were also similar; Meanwhile, the morphous of SGC-7901/HCPT transplanted tumor cells were irregular and in disorder, and the size of the cell nuclei was different from each other. Under the electron microscope, the mitochondria and endoplasmic reticulum of SGC-7901 transplanted tumor cells were nearly normal and no swelling in cell nuclei; Meanwhile the cell nuclei of SGC-7901/HCPT transplanted tumor cells were lightly swelled, a the mitochondria and endoplasmic reticulum were obviously swelled. By MTT assay, compared with SGC-7901 transplanted tumor cells, the resistance index of SGC-7901/HCPT transplanted tumor cells was 9.02±0.78 in HCPT, and resistance index to Adriamycin， Mitomycin C, 5-fluorouracil, and Etoposide was 1.24±0.09, 1.31±0.17, 0.96±0.12, and 1.07±0.16, respectively. Conclusions A transplanted tumor model of SGC-7901/HCPT in nude mice is established successfully， and showing stable drug resistance to HCPT and no cross-resistance to other chemotherapeutics, which can be used for further experiments.
The issue of bacterial drug resistance has remained unresolved, and in recent years, biomimetic nanostructured surfaces inspired by nature have garnered significant attention due to their bactericidal properties demonstrated through mechanical mechanisms. This article reviewed the main research progress in the field of nanostructured mechanical bactericidal surfaces, including various preparation methods for nanostructured surfaces with mechanical bactericidal properties, as well as the basic mechanisms and related physical models of the interaction between bacteria and nanostructured surfaces. In addition, the application of nanostructured surfaces in biomedicine was introduced. Finally, the article proposed the major challenges faced by mechanical bactericidal research and the future development direction.